An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma (NCT00738582), a na phase 2 study. The primary outcome is Number of Participants With Progression Free Survival (PFS) Responders and Non-responders at Month 6.

2. Clinical Question

The brief summary frames the research as asking whether pemetrexed and cisplatin work better when given with the experimental drug MORAb-009. That is a comparative question, but the listed design has a single group and no randomized control. The primary endpoint can describe the observed month-6 response classification in the treated population, but the design described in the record does not establish how that result compares with outcomes under another regimen.

The endpoint definition used radiologist-assessed disease progression or death for the PFS time measure, with imaging measurements based on modified RECIST. Stabilization for at least 6 months counted as a response for this endpoint. The available registry information establishes how the outcome was defined, but not how many participants met that definition or how uncertain the estimate was. Details such as the planned primary analysis and the handling of incomplete assessments are not reported in the registry record.

3. Trial Design

This was a phase 2, open-label, single-group clinical trial. The registry lists 89 participants as enrolled and describes one treatment arm, labeled “Open Label,” receiving pemetrexed, cisplatin and MORAb-009 (amatuximab). Masking was listed as none, and allocation was listed as not applicable. The trial status is completed.

The registry record lists a start date of 2008-12-31 and a primary completion date of 2011-06-30. These dates describe the trial record; they do not supply the timing of individual participants’ follow-up or the duration of treatment. Dose schedules, treatment duration, stopping rules, and follow-up schedules are not reported in the registry record.

The stated primary outcome was the number of participants classified as PFS responders and non-responders at month 6. Secondary outcomes listed were overall response rate, duration of response, time to tumor response, overall survival, and overall progression-free survival. The record lists 7 outcome measures, but does not identify all of them in the available outcome information. It records 0 analyses.

A single-group design can describe outcomes observed among participants receiving the regimen, subject to the endpoint definition and the analysis population. It does not provide a randomized, like-for-like control group for estimating a treatment contrast. The registry does not report a separate control arm or a protocol-based comparison with an external group. Although the brief summary raises a question about whether adding amatuximab improves on pemetrexed and cisplatin, the described design alone cannot answer that comparative question.

The registry record does not report a sample-size justification, a statistical analysis plan, interim analyses, or planned adjustment for prognostic factors. Those details should not be inferred from the phase label or enrollment count.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Combination Therapy

Reasons for not completing this period:

Maintenance Therapy

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary Efficacy Population: all participants who received at least 1 dose of amatuximab and met key eligibility criteria (had measurable disease at screening, had unresectable disease, and had at least 1 response assessment or died after starting treatment with amatuximab). Here, number of participants analyzed are first 77 enrolled participants.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Progression Free Survival (PFS) Responders and Non-responders at Month 6, measured over Month 6.

The primary endpoint counted participants as PFS responders or non-responders at month 6. The underlying PFS definition measured time from the first dose of amatuximab to disease progression or death from any cause. Progression or response was assessed by an independent radiologist using modified RECIST and total tumor measurement from CT or MRI. The total measurement included the pleural unidimensional measure and the measurements of target lesions.

For this endpoint, response meant stabilization of disease for at least 6 months. Modified RECIST progression was defined as an increase of at least 20 percent in total tumor measurement over the nadir measurement, or the appearance of one or more new lesions. Thus, the month-6 classification combines a time condition with radiographic assessment; it is not simply a count of tumor shrinkage.

A binary count can make an endpoint readily interpretable as the number of participants meeting a prespecified classification. However, it compresses the timing and course of disease into responder and non-responder categories. The registry record does not report the two counts, the analysis denominator, or a confidence interval for the endpoint. The endpoint’s use is described, but the record does not explain the rationale for selecting this particular measure or its role in the trial’s design.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation depends first on distinguishing an endpoint definition from an endpoint result. The registry describes who qualifies as a PFS responder and what constitutes progression, but it does not report the resulting responder and non-responder counts. Without those counts and the analysis denominator, the endpoint cannot be summarized as an observed rate or used to assess precision.

What does a binary endpoint count?

General: A binary endpoint places each participant in one of two categories, such as meeting or not meeting a specified response criterion. The count is the number of participants in each category. An event proportion requires both an event count and a denominator from the relevant analysis population. The enrollment figure is not automatically that denominator: eligibility criteria, treatment exposure, and availability of an endpoint assessment can define a different analysis population. In this trial, the primary efficacy population is described, but its size and month-6 category counts are not reported in the registry record.

The endpoint is not simply a measure of tumor shrinkage. The record defines a PFS response as stabilization lasting at least 6 months and defines progression using modified RECIST criteria. PFS itself runs from the first dose of amatuximab until progression or death from any cause. The endpoint therefore depends on follow-up and assessment as well as the radiographic rules. The record does not report the assessment schedule or details of how incomplete follow-up affected classification.

What does a confidence interval convey?

General: A confidence interval describes the precision of an estimate under the assumptions of the method used to calculate it. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. It does not guarantee that the estimate is unbiased, and it does not correct limitations in trial design. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from the listed information.

A statistical test and an effect estimate answer different questions. A test assesses compatibility between data and a specified null hypothesis under a model; an estimate describes the magnitude of an outcome or contrast. Neither is reported for the primary endpoint in the available record. Even if a one-group endpoint count were available, it would describe that group and would not itself supply a randomized comparison of regimens.

Why does the design matter for inference?

General: Random allocation can help create groups that are comparable in expectation, making a between-group contrast more informative about treatment effects. In a single-group study, there is no randomized concurrent group to account for differences in patient characteristics, changes over time, or other influences on outcomes. The design is single-group, with allocation marked not applicable and masking marked none. The registry record does not report a control arm. Therefore, the record’s design supports descriptive interpretation of outcomes in the treated group, not a randomized causal comparison.

Open-label status means masking was not used, according to the registry. For an endpoint involving imaging and radiologist assessment, the record specifically states that an independent radiologist determined progression using modified RECIST. That detail describes the assessment process. The registry does not report further information about blinded review procedures, adjudication, or how disagreements were resolved, so no additional safeguards should be assumed.

What do the planning assumptions mean?

General: A sample-size calculation is a planning exercise based on a target effect, a chosen significance level, allocation, and statistical method. It does not describe the number of events or participants actually observed, and it is not a measure of observed power. The planning illustration associated with the record is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated proportion of the observed effect. For time-to-event calculations, the stated quantity is total events; other calculations are expressed as participants per arm.

Those assumptions do not change the actual design listed in the registry, which is single-group. Equal allocation between two arms is a planning assumption for an illustration, not evidence that this trial randomized participants between two arms. The record does not report the trial’s own sample-size justification or identify a protocol-based target effect. The planning assumptions therefore should not be interpreted as the study’s original design rationale or as evidence that the completed enrollment was adequate for a particular hypothesis.

General: Over-dispersion occurs when variation in observed data exceeds what a model assumes. It can make standard errors too small if ignored. It is often relevant to count data modeled as a distribution, but the registry record does not report a model for the endpoint or any over-dispersion assessment. No conclusion about that issue can be drawn for this trial.

What can the safety counts establish?

General: Counts of participants with events are descriptive unless the groups, follow-up, event definitions, and analysis support a formal comparison. Denominators matter because counts alone do not express how many people were at risk. Even with denominators, observed differences between non-randomized or otherwise non-comparable groups are not automatically treatment effects. The registry’s safety groups have different listed denominators, and the record does not explain their relationship or report an inferential safety comparison. The figures can therefore be described, but not treated as a causal contrast.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary month-6 PFS responder and non-responder count and secondary outcomes for overall response rate, duration of response, time to tumor response, overall survival, and overall progression-free survival. It also reports 7 outcome measures in total, without identifying all of them in the available outcome information. The record lists 0 analyses. This does not establish whether analyses were conducted outside the registry entry; it means analyses are not listed there.

When a study evaluates multiple outcomes or performs repeated tests, the chance of at least one apparently unusual result can increase. General: multiplicity procedures can address that issue by controlling error across a family of comparisons, but the appropriate approach depends on the planned hypotheses and analysis strategy. The statistical plan, hierarchy of outcomes, and any multiplicity adjustment are not reported in the registry record. No adjustment method should be inferred.

The primary efficacy population is defined by treatment exposure, eligibility, and having an assessment or dying after treatment began. The record does not report its size, the number excluded from it, or the month-6 endpoint counts. It also does not state how missing assessments, withdrawals, or other incomplete outcome data were handled. General: missing outcome data can affect both the denominator and the interpretation of an estimated response, especially when the reason for missingness is related to participants’ health or outcomes. Without the missing-data rules and their application, the direction or size of any resulting bias cannot be assessed.

The registry record does not report whether the analysis followed an intention-to-treat approach, a per-protocol approach, or another population definition beyond the stated primary efficacy criteria. That distinction matters because different populations can produce different summaries. No assumption about the analysis population beyond the record’s stated criteria is warranted.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (7.1%), neutropenia (4.5%), atrial fibrillation (4.5%), hypersensitivity (4.5%), hyponatraemia (3.4%).

The registry lists two safety groups. For Amatuximab/Pemetrexed/Cisplatin, 89 participants were at risk for serious adverse events and 38 were affected; 89 were at risk for other adverse events and 89 were affected; and 4 deaths are listed. For the group titled Amatuximab, 56 participants were at risk for serious adverse events and 15 were affected; 56 were at risk for other adverse events and 52 were affected; and 0 deaths are listed.

These values are counts with their listed denominators, not a randomized safety comparison. The record does not explain the relationship between the two groups, why the group sizes differ, or whether participants could appear in both. The figures should not be interpreted as evidence that one treatment caused a higher or lower event burden.

The listed serious-event terms and percentages are dyspnoea, 7.1%; neutropenia, 4.5%; atrial fibrillation, 4.5%; hypersensitivity, 4.5%; hyponatraemia, 3.4%; and anaemia, 3.4%. The registry record does not specify the denominator or detailed counting rules for these percentages. The listed percentages therefore do not permit reconstruction of event counts or a comparison across groups. They describe reported serious-event terms, not the full safety profile.

12. What the Result Does, and Does Not, Mean

The registry record establishes that this was a completed, open-label phase 2 trial with a single group receiving amatuximab, pemetrexed, and cisplatin. It also specifies a month-6 PFS classification, defines response as disease stabilization for at least 6 months, and describes the radiographic progression criteria. These details clarify what the primary endpoint was intended to capture.

The primary endpoint’s observed counts are not reported in the registry record. As a result, the record does not show how many participants were classified as responders or non-responders, what proportion met the definition, or how precise any estimate was. The listed enrollment of 89 is not a substitute for the missing analysis denominator or endpoint result. The record also does not report a confidence interval, test result, or comparative estimate for the primary endpoint.

The single-group design cannot determine from a between-group contrast whether the regimen changed outcomes compared with pemetrexed and cisplatin without amatuximab. The brief summary asks whether the combination works better with the experimental drug, but no randomized comparator is described. An outcome observed among participants receiving the combination, even if reported, would not by itself answer that comparative question.

The safety counts describe events in the named groups, but their different denominators and unexplained relationship limit comparisons. They do not establish that a treatment caused or prevented an event. The registry’s listed serious-event percentages also lack reported denominator details.

Accordingly, the record supports a description of trial design, endpoint definitions, and selected safety counts. It does not provide the primary efficacy result or enough information to reconstruct its statistical analysis. This is a limit on what can be concluded from the registry record, not evidence for a positive or negative treatment effect.

13. Why This Trial Matters Statistically

This trial illustrates a basic distinction in clinical-trial interpretation: defining an outcome is not the same as reporting its observed result. The registry gives a detailed definition for month-6 PFS response, including the time requirement for stabilization and the imaging criteria for progression. But the responder and non-responder counts are not reported. Without those results and their analysis denominator, the endpoint cannot be summarized or assessed for precision.

The design also illustrates the limits of a single-group study when the research question is comparative. The brief summary asks whether adding MORAb-009 to pemetrexed and cisplatin improves on the chemotherapy combination. The listed design has one open-label group and no randomized comparator. That structure can describe outcomes in the treated group, but it does not separate treatment effects from other explanations for the observed outcomes.

Safety reporting raises a related issue: counts need context. The registry lists denominators and event counts for two named groups, but their relationship is not explained and their sizes differ. The counts can be reported as recorded, while a causal or comparative interpretation remains unsupported by the available details.

Finally, the record lists multiple outcome measures but does not report an analysis plan, missing-data approach, multiplicity strategy, or primary endpoint result. These omissions matter because analysis choices and outcome reporting affect what readers can infer. The case emphasizes the value of reporting both prespecified methods and the estimates those methods produce, alongside clear populations and denominators.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation in the registry information is that the primary endpoint is defined but its responder and non-responder counts are not reported. The primary efficacy population is described, yet its size and the number of participants contributing to the month-6 classification are not given. The enrollment count of 89 therefore cannot be assumed to be the endpoint denominator.

The single-group design and absence of a reported randomized comparator limit comparative interpretation. This matters because the stated research question concerns whether the chemotherapy combination works better with amatuximab. A comparison with another regimen is not available in the listed design. Open-label status is recorded, and the endpoint includes radiologist assessment; the record states that an independent radiologist assessed disease using modified RECIST, but does not report further details about review or adjudication.

Several analysis details are not reported in the registry record: the statistical analysis plan, sample-size justification, interim analyses, handling of missing assessments, and any multiplicity strategy. The available information also does not identify all 7 outcome measures or describe all analyses. These gaps prevent evaluation of whether reported analyses, if any, followed prespecified methods.

Safety interpretation is constrained because the two named groups have different denominators and their relationship is not explained. The registry does not provide denominator details for the listed serious-event percentages. Dosing, treatment duration, and follow-up schedules are also not reported, limiting interpretation of exposure and observation time.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma — NCT00738582.
• Registry record last updated 2022-09-22; status last verified 2015-11.
• Results first posted 2022-09-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes NCT00738582, “An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma,” as a completed phase 2, open-label, single-group trial. It lists 89 enrolled participants and a regimen of amatuximab with pemetrexed and cisplatin. The listed start date is 2008-12-31, and the primary completion date is 2011-06-30.

The primary endpoint counted PFS responders and non-responders at month 6; response meant stabilization for at least 6 months. The registry record does not report those counts or the primary analysis denominator. Secondary outcomes include overall response rate, duration of response, time to tumor response, overall survival, and overall progression-free survival.

Selected safety counts are listed for two groups, but the record does not explain their relationship sufficiently for a causal comparison. The statistical analysis plan, missing-data methods, and multiplicity approach are not reported in the registry record.